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Acute liver failure

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Updated 2023 ACG guidelines for the management of acute liver failure.



ALF is a disease characterized by an acute impairment of liver function, leading to encephalopathy and coagulopathy. Hyperacute, acute, and subacute types of liver failure are defined as occurring within 7 days, 7-28 days, and 28 days-6 months of the onset of symptoms, respectively.
Causes of ALF include acetaminophen poisoning, viral hepatitis (hepatitis A, B, C, D, and E, HSV, Ebstein-Barr virus, CMV), AIH, idiosyncratic toxins (tetracycline, halothane, isoniazid, anabolic steroids, phytopharmaceuticals), Wilson's disease, fatty liver of pregnancy, and Budd-Chiari syndrome.
The annual incidence of ALF is estimated at approximately 0.55-0.62 cases per 100,000 person-years.
Disease course
In patients with ALF, apoptosis and necrosis of parenchymal hepatocytes impairs normal liver function, resulting in coagulopathy, hepatic encephalopathy, multiple organ failure, and death.
Prognosis and risk of recurrence
The hospital survival rates of ALF patients treated with liver transplantation and without liver transplantation are 80-86% and 35-48%, respectively.


Key sources

The following summarized guidelines for the evaluation and management of acute liver failure are prepared by our editorial team based on guidelines from the American College of Gastroenterology (ACG 2023), the Society of Critical Care Medicine (SCCM 2023,2020), the American Society for Apheresis (ASFA 2019), the American Gastroenterological Association (AGA 2017), and the European Association for the Study of the ...
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Screening and diagnosis

Definitions and clinical presentation: as per EASL 2017 guidelines, recognize that severe acute liver injury is defined as a syndrome characterized by markers of liver damage (elevated serum transaminases) and impaired liver function (jaundice and INR > 1.5) usually preceding clinical encephalopathy.
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Classification and risk stratification

Prognosis: as per ACG 2023 guidelines, use either the King's College Criteria criteria or the MELD score for prognostication in patients with ALF, recognizing that meeting the King's College Criteria criteria or having a MELD score > 25 represents a high risk for poor outcomes.

Diagnostic investigations

Evaluation for viral hepatitis
As per AGA 2017 guidelines:
Consider testing and treating HSV in patients presenting with ALF.
Consider avoiding routine testing for VZV in immunocompetent patients with ALF.

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  • Evaluation for AIH

  • Evaluation for drug-induced liver injury

  • Evaluation for malignancy

  • Evaluation for Wilson's disease

  • Evaluation for Budd-Chiari syndrome

  • Evaluation for other etiologies

  • Screening for hepatic encephalopathy

  • Viscoelastic testing

Diagnostic procedures

Liver biopsy: as per AGA 2017 guidelines, consider avoiding the routine use of liver biopsy in patients presenting with ALF.

Respiratory support

Supplemental oxygen
As per SCCM 2020 guidelines:
Provide supportive care with supplemental oxygen in the management of patients with hepatopulmonary syndrome, pending possible liver transplantation.
Consider using high-flow nasal cannula over noninvasive ventilation in hypoxic critically ill patients with ALF.

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  • Mechanical ventilation

Medical management

Setting of care: as per EASL 2017 guidelines, obtain prognostic assessment both in the transplant center and at the site of first presentation to allow making decisions in relation to patient transfer to a specialist center at the earliest opportunity.
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  • General principles (goals of care)

  • General principles (precautions)

  • Fluid resuscitation

  • Albumin

  • Vasopressors

  • Inotropes

  • Corticosteroids

  • N-acetylcysteine

  • Management of metabolic derangements

  • Management of coagulopathy

  • Management of infection

  • Management of portopulmonary hypertension

  • Management of vascular complications

  • Management of hepatic encephalopathy

Inpatient care

Clinical and laboratory monitoring
As per SCCM 2020 guidelines:
Consider placing an arterial catheter for BP monitoring in patients with ALF and shock.
Consider obtaining invasive hemodynamic monitoring to guide therapy in patients with ALF and clinically impaired perfusion.

Nonpharmacologic interventions

Nutrition: as per SCCM 2020 guidelines, avoid using a low protein goal in patients with ALF. Consider targeting protein goals comparable to critically ill patients without liver failure (such as 1.2-2.0 g protein/kg dry or ideal body weight per day).
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Therapeutic procedures

Plasmapheresis: as per SCCM 2023 guidelines, consider performing plasma exchange, when available, in critically ill patients with ALF developing hyperammonemia.

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  • RRT

  • Pleurodesis

  • Extracorporeal liver support

Surgical interventions

Liver transplantation, indications: as per EASL 2017 guidelines, assess patients with ALF for emergency liver transplantation by a multidisciplinary team with appropriate experience in this process.
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More topics in this section

  • Liver transplantation (management of deceased donor liver transplant)

  • Liver transplantation (peri-transplant management)

Specific circumstances

Pediatric patients: as per EASL 2017 guidelines, recognize that in pediatric patients:
definition of ALF is not dependent upon the presence of encephalopathy
some etiologies are specific, notably metabolic disorders
transplantation criteria are different compared to adults.

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  • Pregnant patients

  • Patients with HBV infection

  • Patients with mushroom poisoning